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1
Wilce, Alice J. « Understanding the function and mechanisms of intestinal cell kinase in the growth and survival of prostate cancer cells ». Thesis, Queensland University of Technology, 2015. https://eprints.qut.edu.au/85439/1/Alice_Wilce_Thesis.pdf.
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This project was a step forward in discovering the potential role of intestinal cell kinase in prostate cancer development. Intestinal cell kinase was shown to be upregulated in prostate cancer cells and altered expression led to changes in key cell survival proteins. This study used in vitro experiments to monitor changes in cell growth, protein and RNA expression.
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Zhang, Xiaomeng. « Significance and molecular basis of Id-1 in regulation of cancer cell survival and invasion ». Click to view the E-thesis via HKUTO, 2007. http://sunzi.lib.hku.hk/hkuto/record/B39325477.
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Faysal, Joanne M. « The Effects of Hypoxia with Concomitant Acidosis on Prostate Cancer Cell Survival ». Scholarly Repository, 2010. http://scholarlyrepository.miami.edu/oa_theses/69.
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Prostate cancer is the second most common cancer among men in the United States. While treatments for prostate cancer exist, none are curative. As a solid tumor, prostate cancer can grow beyond the diffusion limits of oxygen, thereby resulting in a hypoxic environment. While hypoxia can cause death to a variety of cell types, tumor cells can develop resistance to hypoxia and survive under minimal oxygen conditions. Hypoxia in tumor cells has also been associated with poor prognosis, increased metastasis, and decreased efficacy of chemotherapy. BNIP3, a BH-3 only proapoptotic Bcl-2 family member, has been shown to play an important role in cell death under hypoxic conditions in a variety of cell types. In normoxia, BNIP3 shows little to no expression in both cardiomyocytes and many cancer cell types, but is then upregulated under hypoxic conditions. Previous work in our laboratory provides evidence that hypoxia alone, as well as the concomitant increase in BNIP3 expression, cannot cause death of rat neonatal cardiomyocytes. Instead, our studies found that hypoxia with concomitant intracellular acidosis is required. Further studies indicated that BNIP3 is also necessary for hypoxia-acidosis associated cell death in cardiomyocytes. Our results in rat neonatal cardiomyocytes led us to hypothesize that cell death could be induced in hypoxic prostate cancer cells if concomitant acidosis could be induced. Additionally, our intention was to determine if BNIP3 was required for any prostate cancer cell death that may occur under hypoxia-acidosis conditions.
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Win, Hla Yee. « Role of protein kinase C-iota in prostate cancer ». [Tampa, Fla.] : University of South Florida, 2008. http://purl.fcla.edu/usf/dc/et/SFE0002322.
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Zhang, Xiaomeng, et 張效萌. « Significance and molecular basis of Id-1 in regulation of cancer cell survival and invasion ». Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2007. http://hub.hku.hk/bib/B39325477.
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Soori, Mehrnoosh. « Neuroendocrine differentiation of prostate cancer cells a survival mechanism during early stages of metastatic colonization of bone / ». Access to citation, abstract and download form provided by ProQuest Information and Learning Company ; downloadable PDF file, 105 p, 2009. http://proquest.umi.com/pqdweb?did=1654490661&sid=6&Fmt=2&clientId=8331&RQT=309&VName=PQD.
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Ekman, Maria. « The role of Smad7 and TRAF6 in Prostate Cancer Cell Invasion, Migration and Survival ». Doctoral thesis, Uppsala universitet, Ludwiginstitutet för cancerforskning, 2011. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-159150.
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Transforming growth factor (TGF) β is a tumor suppressor during early tumor development, by inhibiting proliferation and inducing apoptosis. At later stages of cancer, it becomes a tumor promoter, and promotes tumor cell migration and invasion. TGFβ signals via its type II and type I receptors to several downstream signaling pathways. In the present work we have focused on the TRAF6 (tumor necrosis factor receptor-associated factor 6)/ TAK1 (TGFβ activated kinase 1) signaling pathway and the Smad7-dependent activation of p38 in prostate carcinoma cells (PC3U). We found that TGFβ-induced activation of the ubiquitin ligase TRAF6 was needed for cell invasion, by a mechanism that involves activation of the metalloproteinase TNFα converting enzyme (TACE), via protein kinase Cζ (PKCζ). TACE cleaves the TβRI, whereafter the intracellular domain (ICD) translocates to the nucleus, where it binds to the transcriptional co-activator p300 and regulates gene expression, promoting invasion. Interestingly, the translocation of the TβRI ICD was observed in several cancer cell lines and in sections of primary tumors, but not in primary prostate epithelial cells. We also found that Smad7 and adenomatous polyposis coli (APC) are important for TGFβ- and epidermal growth factor (EGF)-induced cell migration in PC3U cells. TGFβ induces the formation of a complex consisting of Smad7, p38, glycogene synthase kinase 3β (GSK-3β), APC and β-catenin, which localizes to the membrane ruffles in the leading edge of migrating cells. The complex links the TβRI to the microtubule system and promotes membrane ruffling and microtubule polarization, which are known to be important for cell migration. In the EGF signaling pathway, Smad7 was found to be important for phosphorylation of the EGF receptor at Tyr1068, for the activation of p38 and JNK, and for induction of membrane ruffles. Smad7 is required for TGFβ-induced activation of p38 and apoptosis. We found that Smad7 forms a complex with p38 and ataxia telangiectasia mutated (ATM), which is important for activation of p53 mediated apoptosis. Many tumor cells including the PC3U cells lack a functional p53, which is one of the reasons to why cancer cells can avoid the tumor suppressor effects of TGFβ.
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Armstrong, Chris. « Inhibition of treatment-induced cell survival signalling enhances radiosensitivity of PTEN-deficient prostate cancer ». Thesis, Queen's University Belfast, 2015. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.680869.
Texte intégralRésumé :
Loss of the tumour suppressor PTEN is a common feature of prostate cancer (PCa) and has recently been identified as a prognostic factor for patient relapse following radiotherapy. Published studies in our laboratory have identified CXCL8 signalling as a mediator of PTEN-depleted disease progression and therapeutic resistance. Therefore, experiments were designed to determine whether ionising radiation (IR) could selectively induce CXCL8 signalling in PTEN-deficient cells. Furthermore, we aimed to determine whether therapeutic targeting of the CXCL8 pathway could enhance PCa cell radiosensitivity. The results in this thesis show how exposure to IR increased gene and protein expression of CXCL8. In addition, inhibiting CXCL8 signalling with receptor-targeted siRNA or peptides increased PTEN-depleted cell sensitivity to IR. In vivo, treatment of PTEN-deficient xenografts with IR and a CXCR1/2-targeted pepducin (x1/2pal-i3) resulted in significant tumour growth delay. Subsequent analysis of tumour material confirmed that this was mediated by modulation of IR-induced anti-apoptotic proteins. Similar to CXCL8 signalling, macrophage infiltration has been associated with enhanced disease progression and poor therapeutic outcomes in prostate cancer patients. Unpublished data in our . laboratory has shown that loss of PTEN can predict for macrophage infiltration in prostate patient samples. Experiments were therefore designed to determine the impact of IR on macrophage-mediated paracrine signalling. Using the THP-1 cell line to model the macrophage component, co-culture systems demonstrated that the presence of microenvironment cells can enhance prostate cancer cell radioresistance. Furthermore, IR was shown to induce secretion of the cytokine TNF-α and this was sufficient to initiate NFKB-mediated upregulation of anti-apoptotic protein expression. Inhibition of cellular inhibitor of apoptosis protein-1 (clAP-1) by Smac-mimetics overcame TNF-α pro-survival effects and reduced cell viability by 50%. In addition, pre-treatment with Smac-mimetics sensitised DU145 cells to ionising radiation following macrophage co-culture.
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BUSA', ROBERTA. « Role of the RNA-binding protein Sam68 in prostate cancer cell survival and proliferation ». Doctoral thesis, Università degli Studi di Roma "Tor Vergata", 2009. http://hdl.handle.net/2108/908.
Texte intégralRésumé :
Il tumore prostatico si sviluppa come una iper-proliferazione dipendente dagli androgeni delle cellule epiteliali ghiandolari e viene inizialmente affrontato con una terapia anti-androgenica. Tuttavia, dopo una regressione iniziale, il tumore si evolve in una forma più aggressiva indipendente dagli androgeni per cui ad oggi non è stata ancora trovata una cura (Grossmann et al., 2001). Nel nostro laboratorio è stata precedentemente descritta l’attivazione della tirosin chinasi Src in un gruppo di tumori prostatici avanzati, correlata alla fosforilazione in tirosina della RNA-binding protein Sam68 (Pronetto et al., 2004) appartenente alla famiglia STAR (Signal transduction and RNA metabolism), coinvolta nello splicing e nel processamento dei pre-mRNA (Lukong and Richard, 2003).
Da qui abbiamo analizzato l’espressione e la funzione di Sam68 in cellule tumorali. Abbiamo osservato che, nei pazienti affetti da PCa, Sam68 è up-regolata sia a livello di mRNA che a livello di proteina. La down-regolazione di Sam68 tramite RNAi o interferire con la sua funzione in vivo con una proteina chimerica (GFP-Sam68GSG ) determinano un rallentamento della proliferazione di cellule tumorali prostatiche e le rendono più suscettibili all’apoptosi indotta da agenti chemoterapici. Questi dati mostrano quindi che l’espressione di Sam68 favorisce la proliferazione delle cellule tumorali di prostata e la sopravvivenza ad agenti chemoterapici (Busà et al., 2007).
Ci siamo poi concentrati sullo studio del ruolo di Sam68 in questi eventi a livello molecolare. Abbiamo osservato che nelle cellule PC3, una linea di tumore prostatico non responsiva agli androgeni, in seguito a trattamento con l’agente chemoterapico mitoxantrone Sam68 rilocalizza all’interno di granuli nucleari. Abbiamo caratterizzato questi granuli nucleari ed abbiamo visto che in essi Sam68 colocalizza con diverse RNA-binding protein, sia appartenenti alla famiglia SR (SC35 e ASF/SF2) sia coinvolte nella risposta cellulare allo stress(hnRNP A1 e TIA1) (Guil et al., 2006). Sam68 si accumula anche in granuli citoplasmatici in cui co-localizza sia con hnRNP A1 che con TIA1, confermando si tratti dei cosiddetti stress granules (SGs). Questi dati suggeriscono che Sam68 faccia parte di una risposta cellulare allo stress “RNA-mediata”. Inoltre, poiché questa proteina è in grado di legare gli mRNA e di mediare lo splicing alternativo di pre-mRNA, abbiamo cercato di identificare i target modulati dal trattamento con il chemoterapico. In particolare ci siamo concentrati sullo splicing alternativo di un target già noto di Sam68, CD44 (Matter et al., 2002). Siamo andati ad analizzare lo splicing alternativo del pre-mRNA di CD44 in seguito a una dose-risposta con il mitoxantrone ed abbiamo riscontrato delle variazioni di splicing di alcuni esoni variabili, in particolare per v5 e v6, che sono noti essere regolati da Sam68 (Matter et al., 2002; Cheng and Sharp, 2006). Per valutare se le differenze osservate sono dovute alla rilocalizzazione di Sam68 effettueremo trattamenti con il chemoterapico su cellule silenziate per Sam68. Abbiamo individuato le vie biochimiche e di trasduzione del segnale che si accendono in risposta al trattamento con il mitoxantrone, la via del DNA damage di ATM e la via delle MAPkinasi indotta da stress di JNK1/2 e p38. Attraverso l’uso di inibitori specifici, per ATM, p38 e JNK, abbiamo osservato che queste vie non sono necessarie per la rilocalizzazione di Sam68. E ‘ dunque possibile che cambiamenti di conformazione della cromatina stimolino l’accumulo si Sam68 ed altri splicing factors nei granuli nucleari.
Infine, alcune evidenze emerse nel corso dei nostri studi suggeriscono un nuovo ruolo di Sam68 nel metabolismo degli rRNA. In un esperimento di co-immunoprecipitazione per Sam68, tra le proteine lin grado di interagire con Sam68 abbiamo identificato Nucleolina, una proteina nucleolare coinvolta nel metabolismo del rRNA (Rickards et al., 2007). Abbiamo confermato quest’interazione e mappato la regione di legame nel dominio carbossi-terminale di Sam68. Inoltre, in un esperimento di co-immunoprecipitazione per Sam68 ed RNA, abbiamo identificato il 18S rRNA tra gli RNA legati da questa proteina. Abbiamo inoltre osservato, attraverso esperimenti di FISH confermati poi da real time PCR, che la down-regolazione di Sam68 determina un aumento significativo dei livelli del pre-rRNA in confronto alle cellule di controllo. Infine esperimenti di ChIP hanno dimostrato che Sam68 è in grado di legare il rDNA a cavallo della regione codificante per il 18S rRNA. Questi risultati suggeriscono un nuovo ruolo di Sam68 nel metabolismo del pre-rRNA.
References:
Busà R, Paronetto MP, Farini D, Pierantozzi E, Botti F, Angelini DF, Attisani F, Vespasiani G, Sette C., Oncogene 2007 26(30):4372-82.
Cheng C, Sharp PA. (2006). Regulation of CD44 alternative splicing by SRm160 and its potential role in tumor cell invasion. Mol Cell Biol. 26(1):362-70.
Grossmann ME, Tindall DJ (2001). Androgen receptor signaling in androgen-refractory prostate cancer. J Natl Cancer Inst. 93:1687-97;
Guil S, Long JC, Cáceres JF. (2006). hnRNP A1 relocalization to the stress granules reflects a role in the stress response. Mol Cell Biol. 26(15):5744-58.
Lukong KE, Richard S (2003). Sam68, the KH domain-containing superSTAR. Bioch. Biophys. Acta 1653: 73-86.
Matter N, Herrlich P, Konig H (2002). Signal-dependent regulation of splicing via phosphorylation of Sam68. Nature 420:691-695.
Paronetto MP, Farini D, Sammarco I, Maturo G, Vespasiani G, Geremia R et al (2004). Expression of a truncated form of the c-Kit tyrosine kinase receptor and activation of Src kinase in human prostatic cancer. Am. J. Path. 164:1243-1251;
Rickards B, Flint SJ, Cole MD, LeRoy G. (2007). Nucleolin is required for RNA polymerase I transcription in vivo. Mol Cell Biol. 27(3):937-48.Prostate carcinoma (PCa) is one of the main causes of death in the western male population. Although initially controlled by anti-androgenic therapies, PCa often evolves to become androgen-insensitive and highly metastatic. A predominant role in the development of androgen-refractoriness is played by the upregulation of signal transduction pathways that allow prostate cancer cells to autonomously produce their own requirements of growth factors and nutrients (Grossmann et al., 2001). The tyrosine kinase Src is frequently activated in advanced human prostate carcinomas and in our laboratory we have observed that its activation correlates with tyrosine phosphorylation of the RNA-binding protein Sam68 (Paronetto et al., 2004), belonging to the STAR family (Signal transduction and RNA metabolism) and involved in RNA metabolism. In the first part of this PhD Thesis, we have investigated the expression and function of Sam68 in human prostate cancer cells. We observed that Sam68 is up-regulated both at protein and mRNA levels in patients affected by PCa. Moreover, it was observed that down-regulation of Sam68 by RNAi in LNCaP prostate cancer cells delayed cell cycle progression, reduced the proliferation rate and sensitized cells to apoptosis induced by DNA-damaging agents. Microarray analyses revealed that a subset of genes involved in proliferation and apoptosis were altered when Sam68 was knocked down in LNCaP cells. Finally, stable cell lines expressing a truncated GFP-Sam68GSG protein, that interacts with endogenous Sam68 affecting its activity, displayed reduced growth rates and higher sensitivity to cisplatin-induced apoptosis, resembling down-regulation of Sam68 by RNAi. Together, these results indicate that Sam68 expression supports prostate cancer cells proliferation and survival to cytotoxic agents (Busà et al., 2007). Stemming from this evidence, we then aimed to investigate the role played by Sam68 in the response to genotoxic drugs such as mitoxantrone (MTX), a topoisomerase II inhibitor.We observed that MTX caused a subcellular re-localization of Sam68 from nucleoplasm to nuclear granules. Co-staining experiments indicated that Sam68-positive nuclear granules are sites of accumulation of several RNA-binding proteins involved in alternative splicing, such as SR proteins like SC35 and ASF/SF2, and TIA-1 and hnRNP A1, involved in cellular stress responses to various stimuli (Guil et al., 2006). Sam68 also accumulated in cytoplasmic granules that were also co-stained with hnRNP A1 and TIA-1, suggesting that these structures are the well described cytoplasmic stress granules (SGs). These data strongly suggest that Sam68 is part of a RNA-mediated stress response of the cell. Thus, we have begun to investigate whether changes in subcellular localization of Sam68 induced by genotoxic drugs affect alternative splicing of Sam68 target mRNAs, such as CD44 (Matter et al., 2002). Preliminary experiments have shown that MTX treatment in PC3 cells induces changes in alternative splicing of CD44 pre-mRNA. In particular, inclusion of variable exons v5 and v6, known to be regulated by Sam68 (Matter et al., 2002; Cheng and Sharp, 2006), was stimulated. We are current extending these studies to determine whether downregulation of Sam68 by RNAi affects these modifications of CD44 alternative splicing caused by MTX Since Sam68 is known to link signal transduction pathways to RNA metabolism (Lukong and Richard, 2003), we asked whether changes in Sam68 subcellular localization induced by MTX are determined by activation of specific signal transduction pathways. Our data show that although MTX triggers activation of DNA damage pathway, through ATM kinase, and stress-induced MAPKs p38 and JNK1/2 pathways, specific inhibition of these pathways did not affect the subcellular relocalization of Sam68. Thus, it is possible that direct changes in the chromatin structure or function trigger the observed accumulation of Sam68 and splicing factors in nuclear granules. Finally, a set of observations performed during our studies implicate Sam68 in nucleolar functions. In a co-immunoprecipitation experiment aimed at the identification of Sam68-interacting proteins in LNCaP cells we found Nucleolin, a nucleolar protein involved in rRNA metabolism (Rickards et al., 2007). This interaction has been confirmed and mapped to the carboxyterminal region of Sam68 by in vitro studies. Moreover, a RNA-protein co-immunoprecipitation experiment revealed that Sam68 binds 18S rRNA These observations lead us to investigate whether Sam68 plays a role in rRNA metabolism. First, we observed by FISH analysis, and then confermed by real time PCR, that downregulation of Sam68 caused a significant increase in the levels of pre-rRNA compared with control siRNA treated cells. Moreover, ChIP assays aimed at determining the site of the association of Sam68 with rDNA in PC3 cells revealed that Sam68 binds the 18S rRNA coding region. Thus, the results presented herein strongly suggest a novel role of Sam68 in the regulation of pre-rRNA maturation. Our current studies are aimed at investigating this hypothesis further. References: Busà R, Paronetto MP, Farini D, Pierantozzi E, Botti F, Angelini DF, Attisani F, Vespasiani G, Sette C., Oncogene 2007 26(30):4372-82. Cheng C, Sharp PA. (2006). Regulation of CD44 alternative splicing by SRm160 and its potential role in tumor cell invasion. Mol Cell Biol. 26(1):362-70. Grossmann ME, Tindall DJ (2001). Androgen receptor signaling in androgen-refractory prostate cancer. J Natl Cancer Inst. 93:1687-97; Guil S, Long JC, Cáceres JF. (2006). hnRNP A1 relocalization to the stress granules reflects a role in the stress response. Mol Cell Biol. 26(15):5744-58. Lukong KE, Richard S (2003). Sam68, the KH domain-containing superSTAR. Bioch. Biophys. Acta 1653: 73-86. Matter N, Herrlich P, Konig H (2002). Signal-dependent regulation of splicing via phosphorylation of Sam68. Nature 420:691-695. Paronetto MP, Farini D, Sammarco I, Maturo G, Vespasiani G, Geremia R et al (2004). Expression of a truncated form of the c-Kit tyrosine kinase receptor and activation of Src kinase in human prostatic cancer. Am. J. Path. 164:1243-1251; Rickards B, Flint SJ, Cole MD, LeRoy G. (2007). Nucleolin is required for RNA polymerase I transcription in vivo. Mol Cell Biol. 27(3):937-48.
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Eng, Grace Tzi Ai. « An investigation of the effect of some stable nitroxide antioxidants in prostate cancer cells ». Thesis, Queensland University of Technology, 2015. https://eprints.qut.edu.au/82982/4/Grace_Eng_Thesis.pdf.
Texte intégralRésumé :
The risk of prostate cancer and disease progression may potentially be increased by oxidative stress. This project examined the stability of nitroxide antioxidants and their effects on cell growth, survival and gene regulation in prostate cancer cells. The novel nitroxide, CTMIO, synthesised here at QUT, was found to have minimal toxicity and modulated the expression of a subset of oxidative stress and antioxidant-related genes distinct from those regulated by a related derivative. This study has provided a step forward in our understanding of the mechanism of action of nitroxides within cells.
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Häggström, Christel. « Metabolic factors and risk of prostate, kidney, and bladder cancer ». Doctoral thesis, Umeå universitet, Urologi och andrologi, 2013. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-83947.
Texte intégralRésumé :
Background: Prostate cancer is the most common cancer in Sweden with around 10,000 new cases every year. Kidney and bladder cancer are less common with 1,000 and 2,000 new cases annually, respectively. The incidence of these cancer sites is higher in developed, than in developing countries, suggesting an association between lifestyle and cancer risk. The aims of this thesis were to investigate body mass index (BMI), blood pressure, and blood levels of glucose, total cholesterol, and triglycerides as risk factors for prostate, kidney, and bladder cancer. Furthermore, we aimed at assess probabilities of prostate cancer and competing events, all-cause death, for men with normal and high levels of metabolic factors. Material and methods: This thesis was conducted within the Metabolic Syndrome and Cancer project (Me-Can), a pooled cohort study with data from 578,700 participants from Norway, Sweden, and Austria. Data from metabolic factors were prospectively collected at health examinations and linked to the Cancer and Cause of Death registers in each country. Results: High levels of metabolic factors were not associated with increased risk of prostate cancer, but high levels of BMI and blood pressure were associated with risk of prostate cancer death. The probability of prostate cancer was higher for men with normal levels of metabolic factors compared to men with high levels, but the probability of all-cause death, was higher for men with high levels than for those with normal levels. For both men and women, high levels of metabolic factors were associated with increased risk of kidney cancer (renal cell carcinoma). Furthermore, blood pressure for men and BMI for women were found as independent risk factors of kidney cancer. High blood pressure was associated with an increased risk of bladder cancer for men. Conclusions: High levels of metabolic factors were associated to risk of kidney and bladder cancer and to death from kidney, bladder, and prostate cancer. Compared to men with normal levels, men with high levels of metabolic factors had a decreased probability of prostate cancer but an increased probability of all-cause death.Ytterligare forskningsfinansiärer: World Cancer Research Fund (2007/09) och Wereld Kanker Onderzoek Fonds (R2010/247)
Me-Can
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Low, Christopher Gah-Mun. « The role of BIRC6, a member of the inhibitor of apoptosis protein (IAP) family, in the survival of human prostate cancer cells ». Thesis, University of British Columbia, 2010. http://hdl.handle.net/2429/29564.
Texte intégralRésumé :
Prostate cancer is the most commonly diagnosed cancer and third leading cause of cancer deaths in Canadian men. Prostate cancers typically begin as androgen-dependent tumours susceptible to growth arrest/apoptosis induced by ablation of androgens. Although initially effective, androgen ablation frequently leads to the development of castration-resistant (androgen-independent) prostate cancer, which is generally also resistant to other available treatments. Development of castration-resistant prostate cancer is characteristically associated with marked increases in resistance to apoptosis. BIRC6 is a member of the Inhibitors of Apoptosis Protein (IAP) family which protects a variety of cancer cell lines from apoptosis. In the present study, we have investigated whether BIRC6 plays a role in prostate cancer and could potentially be useful as a novel therapeutic target. Analysis of a variety of human prostate cancer cell lines and clinical specimens for BIRC6 protein expression, using Western blot and immunohistochemical analyses, respectively, showed that BIRC6 protein is markedly expressed by the prostate cancer cell lines and by clinical cancer specimens, as distinct from benign prostate cells/tissue. In addition, analysis of the clinical specimens showed that elevated BIRC6 protein expression was found to be particularly associated with cancers of Gleason score 6-8 and with the development of castration-resistant disease. Specific, siRNA-induced reduction of BIRC6 expression in LNCaP cells led to a marked reduction in cell proliferation, associated with an increase in apoptosis markers and a decrease in autophagosome markers, indicating that BIRC6 plays a major protective role in the proliferation of LNCaP cells by inhibiting apoptosis and perhaps by enhancing autophagy. Taken together, the data suggest an important role for BIRC6 in prostate cancer growth and progression, particularly, in the development of treatment resistance. In conclusion, this study indicates - for the first time - that the BIRC6 gene and its product are potentially valuable targets for therapy of human prostate cancers. BIRC6-targeting drugs may be especially useful for sensitization of cancer cells in combination therapy.
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Sharpe, Benjamin Peter. « Prostate cancer stem cells : potential new biomarkers ». Thesis, University of Bath, 2016. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.698969.
Texte intégralRésumé :
Prostate cancer is a leading cause of cancer-related death in men, and while many men diagnosed with the disease will have an indolent clinical course, 20-25% of men will experience disease recurrence which is invariably lethal. There is an urgent need for prognostic biomarkers that will predict disease recurrence and risk-stratify patients upon diagnosis, allowing for personalised therapies. This thesis attempts to identify new prognostic biomarkers for prostate cancer and investigates their patterns of protein expression in human primary prostate tumour tissue. Cancer stem cells are cancer cells thought to be uniquely capable of self-renewal and tumorigenicity, and may have a role in tumour recurrence. Using a literature searching approach, potential biomarkers related to stem cells, cancer stem cells or recurrence in prostate cancer were identified, and ALDH7A1, BMI1, SDC1, MUC1-C, Nestin and ZSCAN4 were chosen for investigation. An in silico approach was also used for biomarker identification, with RS1 and SLC31A1 selected as their mRNA was found to be upregulated in recurrent tumours. The expression patterns of all 7 potential biomarkers were examined by immunohistochemistry on prostate tumour tissue and benign tissue from prostate biopsies and prostatectomies. BMI1, ALDH7A1, MUC1-C and Nestin showed no relationship to recurrence or other clinical features. RS1 protein levels increased in patients with recurrence within 5 years, negatively correlated with AR expression, and a meta-analysis showed that the RS1 gene was amplified in up to 32% of castration-resistant prostate tumours. ZSCAN4 was heterogeneously expressed in a subset of 26% of prostate tumours with unclear characteristics and was not expressed in benign tissue, but was not associated with recurrence. Finally, SDC1 expression was lost in tumour epithelium, but a population of unidentified SDC1-expressing cells were found in the stroma of a third of tumours, and an increased burden of these cells was associated with primary Gleason pattern 5 tumours. These cells do not overlap with common epithelial, mesenchymal or stromal lineages, but may be migratory. In summary, the data presented in this thesis identifies 3 potential new biomarkers for prostate cancer, and provides the basis for future characterisation of their wider roles in the disease.
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Trapika, I. Gusti Made Gde Surya Chandra. « Anti-Cancer Activity of Dendrobium chrysotoxum in human prostate cancer cells ». Thesis, The University of Sydney, 2020. https://hdl.handle.net/2123/22501.
Texte intégralRésumé :
Dendrobium is one of the most valuable herbs in traditional Chinese medicine (TCM). It’s bibenzyl compounds demonstrate promising anti-cancer properties. Prostate cancer is the second most common cancer in men with estimated 1.1 million new cases and 0.8 million deaths per year in 2012. While Dendrobium’ anti-cancer activities has been explored in several cancer cell lines, the investigation of their bioactivity on prostate cancer is generally limited. Therefore, this thesis examines bioactivity and molecular mechanisms of selected Dendrobium species and their isolated chemical constituents in the three prostate cancer cell lines, LNCaP, an androgen dependent prostate cancer cell line, PC3 and DU-145, two non-dependent androgen cell lines. The study began with the screening of ten Dendrobium species commonly used in TCM practice, Dendrobium anosnum, D. aphyllum, D. devonianum, D. officinale, D. nobile, D. loddigesi, D. parisii, D. fimbriatum, D. aduncum, and D. chrysotoxum. Bioassay-guided fractionation techniques were applied to isolate and characterise the active compounds of the Dendrobium species that possess anti-cancer activity against the three prostate cancer cells. The crude extract of all ten Dendrobium species showed promising inhibitory effects on the three selected prostate cancer cell lines at a concentration of 20µg/mL. D. chrysotoxum exhibited the strongest anti-cancer activity which was then subjected to further investigation. Isolation, purification and elucidation procedures revealed that erianin is the predominant bibenzyl compound in D. chrysotoxum and is responsible for its anti-cancer activity. Our initial findings confirmed that erianin, is highly abundant in D. chrysotoxum, whereas other studies showed it is present in a much lower amounts in other Dendrobium species. Dendrobium species vary widely in their chemical constituents, and several factors including geographic, climatic and season of harvesting influence their quantity and quality. Hence, the almost exclusive presence of erianin in D. chrysotoxum could be applied for standardization and quality control of the anti-cancer properties of this Dendrobium species. Erianin exhibited anti-cancer activity in prostate cancer cells with an IC50 value below 50nM signifying its potency as a promising anti-cancer agent. At 24 hours of treatment, the IC50 of erianin for LNCaP cells is about twice the IC50 of PC3, while at a longer treatment times, the IC50 values of the two prostate cancer cells lines were similar, of 32.96nM for LNCaP and 36.06nM for PC3, at 72 hours of treatment. While erianin exhibits strong inhibition of cancer cell viability, erianin has no effect on the migration of either LNCaP and PC3 cells. The anti-cancer mechanism of erianin was further explored on LNCaP and PC3 cells representing the two different types in androgen dependence of prostate cancer. Erianin showed a different anti-cancer mechanism of action between the two prostate cancer cell lines. In androgen sensitive LNCaP, erianin induced apoptosis and autophagy. However, in androgen insensitive PC3 cells it induced autophagy and G2/M phase arrest. This thesis then compares erianin’s anti-cancer mechanism in prostate cancer cells with the mechanisms that have been identified in other previously studied cancer cell lines and discusses the underlying mechanism of erianin anticancer bioactivity. The anti-cancer activity of erianin on prostate cancer cell lines through induced apoptosis, autophagy and cell cycle arrest aligns with its bioactivity in other cell lines. Our study lays the essential findings of the potency of erianin against both androgen dependent and androgen independent prostate cancer cells, further elucidation of the mechanism and validation with in vivo experiments are required.
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Davoodpour, Padideh. « 2-ME-Induced Apoptotic Signalling in Prostate Cancer PC3 Cells ». Doctoral thesis, Uppsala : Acta Universitatis Upsaliensis : Univ.-bibl. [distributör], 2005. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-6136.
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Klossner, Daniel Patrick. « Improving cryosurgical ablation of advanced state prostate cancer through identification of molecular targets in a prostrate cancer cell model ». Diss., Online access via UMI:, 2007.
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Xi, Sichuan. « Oncostatic actions of melatonin on tumor cell growth in the LNCaP model of human prostate cancer ». Thesis, Hong Kong : University of Hong Kong, 2000. http://sunzi.lib.hku.hk/hkuto/record.jsp?B22226898.
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McEwen, Alexander. « Effects Of Tumour Cell Lines On Endothelial Cell Survival ». Thesis, The University of Sydney, 2001. http://hdl.handle.net/2123/4970.
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Tam, Chun-wai, et 談振偉. « Combating prostate diseases with ethnobotanical drugs : inhibition of prostate cancer cell proliferation by SawPalmetto (Serenoa repens) extracts ». Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2003. http://hub.hku.hk/bib/B29188969.
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Ashford, Anne Louise. « The role of the protein kinase DYRK1B in cancer cell survival and cell cycle control ». Thesis, University of Cambridge, 2014. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.648671.
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Hartley, Strachan. « Prolactin mediated activation of survival pathways in human breast cancer cells ». Thesis, McGill University, 2002. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=29440.
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This study investigates the role of prolactin (PRL) as an autocrine/paracrine survival and/or growth factor in the human breast cancer cell line T47D and the signaling pathways that mediate this function. Utilizing an oligonucleotide antisense to human PRL (hPRL) mRNA to inhibit endogenous PRL production in T47D cells, we found that PRL contributes to the viability of the T47D cells. Furthermore, exogenous PRL stimulation mediates the activation of the protein kinase B/Akt (PKB/Akt) in the mammary epithelial cell lines HC11 and MCF-10, as well as T47D cells. PRL stimulation led to the phosphorylation of the pro-apoptotic protein Bad, a member of the Bcl-2 family, as well as the phosphorylation and subsequent cytoplasmic sequestration of FKHRL1, a member of the forkhead family of transcription factors. Utilizing the P13kinase inhibitor LY294002, the Jak2 inhibitor Ag490, and the Src kinase inhibitor PP2, we illustrated that PRL-mediated activation of PKB/Akt was dependent on both P13kinase and Src kinase activity, but independent of Jak2 kinase activity. (Abstract shortened by UMI.)
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Israel, Karen E. « Growth arrest and apoptotic induction in RRR-[alpha]-tocopheryl succinate-treated LNCaP and PC-3 human prostate cancer cell lines / ». Digital version accessible at:, 1999. http://wwwlib.umi.com/cr/utexas/main.
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Hastie, C. L. « Differential protein expression on the cell surface of normal epithelial and prostate cancer cells ». Thesis, University College London (University of London), 2007. http://discovery.ucl.ac.uk/1445546/.
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Prostate cancer is the most frequently diagnosed cancer in men in Western countries. Clinically localized disease can be cured with surgery or radiotherapy, but once the disease has advanced or spread, there are no curative treatments. The aim of this thesis is to compare protein expression in a pair of normal epithelial and prostate cancer cells derived from the same patient and to determine the effect of interferon y on this expression pattern. Proteins that are differentially expressed or change in expression in response to y interferon might be of clinical value as biomarkers or therapeutic targets. Biotin labelling followed by avidin chromatography was used to obtain membrane protein enriched lysates from a pair of cell lines derived from normal epithelium (1542 NPX) and prostate cancer (1542 CP3TX) from the same patient. These proteins were resolved and identified using SDS PAGE, coomassie staining and mass spectrometry. The same protocol was used to identify proteins differentially expressed on stimulation with interferon y. The proteins identified were subject to further analysis, particularly annexin II (All), which was interferon-regulated. The expression of this protein was down regulated in the cancer cell line within four hours of interferon y stimulation. This expression pattern was found to be cell surface specific as the total cellular expression of All remained unchanged, as confirmed by immunofluorescence. All down regulation also reduced the invasive potential of the cancer cells. Re-introduction of All into LNCaP cells, which do not express the protein, led to an increase in their invasive capacity. The mechanism regulating this cell surface specific effect was explored. It was discovered that inhibition of the ATP binding cassette transporter ABCA1 prevented surface AH expression. Protection of ABCA1 from calpain mediated degradation, maintained AH expression even in the presence of interferon y. These findings led to the development of a model of interferon y action on All involving phosphorylation of ABCA1 as a signal for targeted degradation by calpain II.
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Carlini, V. « CELL CYCLE AND MIGRATION CONTROL IN PROSTATE AND COLON CANCER CELLS BY CLIC1 PROTEIN ». Doctoral thesis, Università degli Studi di Milano, 2017. http://hdl.handle.net/2434/522972.
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The intracellular chloride channel 1 (CLIC1) is a metamorphic protein, belonging to a recently discovered and still largely unexplored ion channel family. It displays the unique characteristic of being expressed both in a cytoplasmic and in a transmembrane form, the latter able to form a chloride selective ion channel. One of the main factors known to regulate this membrane insertion is the increase of oxidative level of the cells.
If on one hand, the transient CLIC1 functional expression in the membrane could mediate several physiological cell responses, on the other hand, its chronic membrane translocation can lead to severe pathological conditions, including cancer. In particular two tumors, prostate cancer (PCa) and colon cancer (CRC), are characterized by elevated oxidative level and growing scientific evidence have suggested the involvement of CLIC1 in the tumorigenesis of these diseases.
PCa and CRC are two of the most diffuse cancers and a leading cause of tumor fatality worldwide. Detecting the disease in a very early stage and finding a treatment able to prevent metastasis are critical clinical challenges to achieve a successful treatment for these malignancies.
This thesis was focused in the direction of understanding the possible role of CLIC1 in the development and progression of PCa and CRC.
Results obtained have shown that CLIC1 functional expression in plasma membrane occurs selectively in malignant cells, compared to benign or normal cells. Moreover, it has been demonstrated that CLIC1 membrane chloride current promotes proliferation, cell cycle progression from G1 to S phase and migration of cancer cells. All these findings suggest that CLIC1 may actively contribute to development of PCa and CRC and their progression towards a more aggressive form.
It can be reasonably hypothesize that elevated oxidative levels present in cancer cells compared to normal cells cause the chronic overexpression of CLIC1 in the plasma membrane only of malignant cells. Therefore, targeting this protein could make it possible to hit selectively the tumor cells without damaging their normal counterpart. In this scenario, CLIC1 appears not only as a promising pharmacological target but also as a suitable biomarker.
The only effective inhibitor of CLIC1 activity to date identified is highly toxic in vivo. For this reason, finding other compounds able to specifically block the channel but causing negligible side effects is necessary. In light with this purpose, our laboratory has recently proposed the anti-diabetic drug metformin as CLIC1 channel blocker.
Results obtained have demonstrated that metformin displays a significant antitumoral activity on PCa and CRC cells, inhibiting both cell proliferation and migration. This anti-neoplastic effect is dependent on the inhibition of CLIC1 channel together with other intracellular targets.
Overall these findings provide new support on the antineoplastic role of metformin and encourage the research of more specific and more effective compounds for CLIC1 channel, in order to minimize side effects.
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Tang, Kai Dun. « Dissecting the prostate cancer stem cell niche inside the bone marrow ». Thesis, Queensland University of Technology, 2015. https://eprints.qut.edu.au/88935/1/Kai%20Dun_Tang_Thesis.pdf.
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Prostate cancer frequently metastasizes to bone, which becomes incurable; yet how cancer cells manage to migrate and grow inside the bone remains unknown. In this study I have discovered that both bone and fat cells within the bone marrow actively promote the survival and expansion of prostate cancer cells, and have subsequently developed approaches that can effectively inhibit these processes. Therefore, my work offers opportunities for the development of new prognostic and therapeutic approaches against metastatic prostate cancer and have the potential for improving the treatment outcome of the patients.
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Shyam, Sunitha. « S-phase Synchronization Promotes Chemoradiotherapy-induced Apoptosis in Prostate Cancer Cell Lines ». Kent State University / OhioLINK, 2007. http://rave.ohiolink.edu/etdc/view?acc_num=kent1185835523.
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Wang, Man-Tzu. « Roles of Nanog, a transcription factor for self-renewal of embryonic stem cells, in prostate tumor initiation and chemoresistance ». OpenSIUC, 2010. https://opensiuc.lib.siu.edu/dissertations/237.
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Prostate cancer is one of the most common cancers affecting one of every six men in United States. It is increasingly appreciated that tumor or cancer stem cells are the cells responsible for initiating tumor formation and therefore should be targeted for eradication in cancer treatment. But the mechanism involved in the acquisition of unlimited self-renewal and tumor initiation by cancer stem cells is unknown. Nanog, along with Oct3/4 and Sox-2, constitute the core transcriptional circuitry for the maintenance of stemness in embryonic stem cells. Herein we report that Nanog expression was detected at mRNA and protein levels in prostate cancer cells. The Nanog-expressing LNCaP-T and DU145 cells were enriched by infection with lentiviruses expressing GFP under the control of Nanog promoter. The Nanog-enriched prostate cancer cells had stronger expressions of stem and progenitor cell surface markers, including CD44 and CD133, when compared with those in the control group. Colony formation assay found that the Nanog-enriched LNCaP-T and DU145 cells formed more holoclones and prosta-spheres, which contained more self-renewing cells, than the control cells did. On the other hand, knockdown of Nanog in DU145 or LNCaP-T cells, via shRNAs, reduced their ability to form holoclones. Instead, most clones derived were meroclone and paraclones as result of increased differentiation and senescence due to knockdown of Nanog. When injected into mice, Nanog-enriched DU145 cells were found to possess increased tumorigenic potentials when compared to the vector controls. On the other hand, LNCaP-T cells with Nanog knocked down did not form tumors, while the vector controls readily formed tumors. Taken together, our data suggest an essential role for Nanog in the self-renewal and tumor initiation of prostate cancer cells. Chemotherapy is the major salvage therapeutic modality available for the patients with advanced cancers. However, drug resistance by some prostate cancer cells is a major barrier to efficacious chemotherapy. It has been increasingly appreciated that cancer stem cells are responsible for resistance to chemo- or radio-therapy, in addition to tumor initiation. However, the mechanisms involved remain unknown. In this study, we examined whether Nanog plays an essential role of Nanog in resistance to chemotherapy. In the surviving fractions of prostate cancer cells, we found increased levels of Nanog protein when compared to the cells treated with solvent control. To determine the role of Nanog in resistance of prostate cancer cells, we marked and enriched Nanog-expressing prostate cancer DU145 and LNCaP-T cells using a reporter gene under control of 2.5 kb hNanog1 promoter. When compared to the control, the prospectively enriched Nanog-expressing cells presented increased resistance to Taxol, vinblastine, and doxorubicin. Profiling of genes in drug resistance and metabolism revealed a marked increase in the mRNA level of ATP-binding cassette (ABC) efflux transporters B1 and G2 in tumor cells enriched with endogenous Nanog expression. The increased expression of ABCB1 and ABCG2 at protein levels in Nanog expressing cells was confirmed by Western blot and immunocytochemistry. Inhibition of ABCB1 activities sensitized Nanog expressing cells toward Taxol and vinblastine, and to less extent, doxorubicin. Blocking of ABCG2 activity sensitized Nanog expressing cells toward doxorubicin, but not Taxol and vinblastine. In addition, the tumor cells enriched with Nanog expression showed reduced apoptosis in response to Taxol treatment. Interestingly, Nanog-enriched prostate carcinoma cells displayed aberrantly activated â-catenin signaling, which is potentially associated with their increased chemo-resistant ability as well as the increased acquisition of epithelial to mesenchymal transition. In summary, Nanog is expressed in prostate cancer cells, especially in those positive for stem/progenitor markers. Enrichment of Nanog expressing cells led to enrichment of tumor cells with increased tumor initiating ability and increased resistance toward chemotherapy. Knockdown of Nanog reduces tumor initiating ability of prostate cancer cells and further sensitizes them toward chemotherapy. The gain-of-function and loss-of-function studies suggest an essential role of Nanog for prostate cancer cells to initiate tumor formation and resist chemotherapy.
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Randle, Diandra Dominique. « Snail mediates cell invasion through uPa-uPar and mark signaling in human prostate cancer cells ». DigitalCommons@Robert W. Woodruff Library, Atlanta University Center, 2014. http://digitalcommons.auctr.edu/dissertations/1648.
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Epithelial-mesenchymal transition (EMT) is a process by which cancer cells acquire mesenchymal properties, such as induction of vimentin, while epithelial-associated genes like E-cadherin are lost. This enables the cells to be more metastatic. Factors that can induce EMT include growth factors like transforming growth factor -P (TGF-P) and epidermal growth factor (EGF), and transcription factors like Snail. Snail-induced EMT promotes migration and invasion and we hypothesized that this may be mediated by urokinase (uPA) and its receptor (uPAR) activities. LNCaP, 22Rvl and ARCaP human prostate cancer (CaP) cells stably transfected with constitutively active Snail displayed increased cell invasion as compared to the empty vector control (Neo). Superarray analysis revealed an up-regulation in uPA and uPAR RNA expression in Snailtransfected ARCaP cells as compared to Neo control. Next, the protein expression levels of Snail, uPA, and uPAR were measured by western blot analysis in various prostate cancer cell lines which showed that overexpression of Snail increased uPA and uPAR protein levels. The activity of uPA in conditioned media was measured using an ELISA assay which revealed that uPA activity was elevated in LNCaP, 22Rvl and ARCaP cells overexpressing Snail. Additionally, transient silencing of uPAR in ARCaP cells overexpressing Snail using siRNA resulted in abrogation of Snail-mediated invasion. Snail overexpression was associated with increased ERK activity and antagonism of this activity with MAPK inhibitor, UO126, inhibited cell invasion and decreased uPA activity. Therefore, Snail-mediated cell invasion in human prostate cancer cells may occur via the regulation of uPA/ uPAR and the MAPK signaling pathways.
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Fiñones, Rita Roces. « Inducing pluripotency and immortality in prostate tumor cells a stem cell model of cancer progression / ». Diss., [La Jolla] : University of California, San Diego, 2009. http://wwwlib.umi.com/cr/ucsd/fullcit?p3344826.
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Thesis (Ph. D.)--University of California, San Diego, 2009.Title from first page of PDF file (viewed June 16, 2009). Available via ProQuest Digital Dissertations. Vita. Includes bibliographical references.
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Jiang, Wen, Lin Ye, Andrew Sanders, Fiona Ruge, Howard Kynaston, Richard Ablin et Malcolm Mason. « Prostate transglutaminase (TGase-4, TGaseP) enhances the adhesion of prostate cancer cells to extracellular matrix, the potential role of TGase-core domain ». BioMed Central, 2013. http://hdl.handle.net/10150/610200.
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BACKGROUND:Transglutaminase-4 (TGase-4), also known as the Prostate Transglutaminase, is an enzyme found to be expressed predominately in the prostate gland. The protein has been recently reported to influence the migration and invasiveness of prostate cancer cells. The present study aimed to investigate the influence of TGase-4 on cell-matrix adhesion and search for the candidate active domains] within the protein.METHODS:Human prostate cancer cell lines and prostate tissues were used. Plasmids that encoded different domains and full length of TGase-4 were constructed and used to generate sublines that expressed different domains. The impact of TGase-4 on in vitro cell-matrix adhesion, cell migration, growth and in vivo growth were investigated. Interactions between TGase-4 and focal adhesion complex proteins were investigated using immunoprecipitation, immunofluorescence and phosphospecific antibodies.RESULTS:TGase-4 markedly increased cell-matrix adhesion and cellular migration, and resulted in a rapid growth of prostate tumours in vivo. This effect resided in the Core-domain of the TGase-4 protein. TGase-4 was found to co-precipitate and co-localise with focal adhesion kinase (FAK) and paxillin, in cells, human prostate tissues and tumour xenografts. FAK small inhibitor was able to block the action mediated by TGase-4 and TGase-4 core domain.CONCLUSION:TGase-4 is an important regulator of cell-matrix adhesion of prostate cancer cells. This effect is predominately mediated by its core domain and requires the participation of focal adhesion complex proteins.
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Donthula, Vinitha Islam Naz E. « Effects of nano-second pulsed electric fields (nsPEF) on human prostate cancer cell line - LNCaP ». Diss., Columbia, Mo. : University of Missouri--Columbia, 2008. http://hdl.handle.net/10355/5665.
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The entire thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file; a non-technical public abstract appears in the public.pdf file. Title from PDF of title page (University of Missouri--Columbia, viewed on September 22, 2009). Thesis advisor: Dr. Naz E. Islam. Includes bibliographical references.
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McEwan, David George. « Cyclic AMP modulation and its effects on chemo-resistant colon cancer cell proliferation and survival ». Connect to e-thesis, 2007. http://theses.gla.ac.uk/81/.
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Thesis (Ph.D.) - University of Glasgow, 2007.Thesis submitted in part fulfilment of the Ph.D. to The Beatson Institute for Cancer Research, Faculty of Medicine, University of Glasgow, 2007. Includes bibliographical references. Print version also available.
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Chen, Jia, et 陳珈. « Identification of tumor-associated proteins in human prostatic epithelial cell lines & ; squamous cell carcinoma of head and neck byproteomic technology ». Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2004. http://hub.hku.hk/bib/B31519362.
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Petitprez, Florent. « Integrated analysis and clinical impact of immune and stromal microenvironments in solid tumors Quantitative analyses of the tumor microenvironment composition and orientation in the era of precision medicine Transcriptomic analysis of the tumor microenvironment to guide prognosis and immunotherapies Tumor microenvironment quantification tool draws a comprehensive map of the tumor microenvironment of non-hematologic human cancers The mMCP-counter method to estimate abundance of tissue-infiltrating immune and stromal cell populations using gene expression in murine samples Immune sub-classes in sarcoma predict survival and immunotherapy response Intra-tumoral tertiary lymphoid structures are associated with a low risk of hepatocellular carcinoma early recurrence Association of IL-36γ with tertiary lymphoid structures and inflammatory immune infiltrates in human colorectal cancer Immune-based identification of cancer patients at high risk of progression Tumor-infiltrating and peripheral blood T-cell immunophenotypes predict early relapse in localized clear cell renal cell carcinoma PD-L1 expression and CD8+ T-cell infiltrate are associated with clinical progression in patients with node-positive prostate cancer Intratumoral classical complement pathway activation promotes cancer progression ». Thesis, Sorbonne Paris Cité, 2018. http://www.theses.fr/2018USPCB104.
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Les tumeurs sont composées de cellules malignes et d'une grande variété de cellules non-tumorales, en particulier des cellules immunitaires qui forment le micro-environnement tumoral (MET). Il a été démontré que la composition du MET était associée au devenir clinique des patients, en termes de survie et de réponses thérapeutiques. Avec le développement récent des immunothérapies qui ciblent des éléments spécifiques du MET, l'immunité anti-tumorale a soulevé un intérêt majeur. Plusieurs méthodologies ont été mises au point afin d'étudier la composition du MET, avec une précision toujours plus grande. En particulier, des méthodes comme MCP-counter permettent d'exploiter les données transcriptomiques de la tumeur entière afin de quantifier les différentes populations qui composent le MET. Le volet méthodologique de ce travail de thèse a ainsi consisté à proposer une amélioration de MCP-counter, en particulier pour l'analyse de données RNA-Seq. Une adaptation de la méthode pour des données issues de modèles murins (mMCP-counter) est également proposée. MCP-counter permet d'analyser rapidement le MET de larges séries de tumeurs. Un second volet de cette thèse consiste en l'application de cette méthode pour établir une classification immunitaire des sarcomes des tissus mous, un type de cancer rare, hétérogène et agressif. Cette classification immunitaire a permis de mettre en évidence des groupes de tumeurs faiblement ou fortement infiltrés, ainsi qu'un groupe marqué par une forte vascularisation. De manière intéressante, la classification immunitaire permet de prédire la réponse des patients aux immunothérapies. Ce travail a aussi démontré un rôle important des structures lymphoïdes tertiaires (SLT). Les SLT sont des structures de type noeud lymphatique composées de lymphocytes B et T qui se forment dans la tumeur ou à proximité de celle-ci. Au sein des SLT, une réponse immunitaire anti-tumorale peut se former et maturer. L'intérêt porté aux SLT est de plus en plus important pour de nombreux types de cancers. Dans la plupart des types de cancer, une forte infiltration de la tumeur par des lymphocytes T, en particulier CD8+, est associée à une meilleure survie des patients. Cependant, le carcinome rénal à cellules claires et le cancer de la prostate sont des exceptions à cette règle. En effet, dans ces deux cancers urologiques, la présence dans la tumeur de lymphocytes T est associée à une survie plus courte des patients, ainsi qu'à une rechute et une progression plus précoce. Ces exceptions sont détaillées dans une troisième partie de cette thèse, par une description minutieuse du MET, ainsi que par l'analyse de l'implication du système du complément. Dans leur ensemble, les résultats présentés dans cette thèse démontrent qu'en combinant différentes méthodes d'analyse, in silico, in situ et in vivo, il est possible d'obtenir une vision extrêmement complète du MET. La connaissance des types cellulaires présents dans la tumeur ainsi que leur orientation fonctionnelle permet de guider le soin apporté aux patients et d'améliorer leur devenir clinique. La description complète du MET ouvre la voie à une médecine personnalisée pour les patients atteints de cancerTumors are composed not only of malignant cells but also contain a vast variety of non-malignant cells, notably immune cells forming the tumor microenvironment (TME). The composition of the TME was shown to be associated with clinical outcome for cancer patients, in terms of survival and therapeutic responses. With the relatively recent development of immunotherapies targeting specific elements of the TME, tumor immunology has risen a strong interest and holds a strong therapeutic potential. Several methodologies have been developed to study the composition of the TME with an increased precision. Notably, some methods such as MCP-counter enable the use of the tumor bulk transcriptome to quantify cell populations composing the TME. The methodological aspect of this PhD project consisted in setting up an enhanced version of MCP-counter that can be readily applied to RNA-Seq data, as well as propose an adaptation of the method for mouse models. Using MCP-counter, the TME of large series of tumors can be easily analyzed. The application part of this PhD work consisted of applying MCP-counter to establish an immune-based classification of soft-tissue sarcoma, a rare, aggressive and heterogeneous cancer type. The immune classification notably allowed to identify immune low and high groups, and a group characterized by a strong vasculature. Interestingly, the classification was notably found to be predictive of the patients' response to immunotherapies. It also highlighted an important role of tertiary lymphoid structures (TLS). TLS are lymph-node-like structures composed of T and B cells that form within the tumor or in close proximity. They are a site of formation and maturation of antitumoral immune responses. TLS are raising a growing interest in many malignancies. In most cancer types, a strong infiltration by T cells, in particular CD8+ T cells, is associated with a favorable clinical outcome. However, clear-cell renal cell carcinoma and prostate cancer are exceptions to this general rule. Indeed, in these urological cancers, an increased infiltration by T cells is associated with a decreased patient survival and with earlier relapse and disease progression. In a third part of this thesis, these exceptions are investigated with more details by scrutinizing the TME, and questioning the implication of the complement system. Overall, this thesis presents how the combination of several analysis methods, in silico, in situ and in vivo, can help achieve an extremely precise description of the TME. Knowing accurately what cell populations and what their functional orientation can help guide patients care and improve clinical outcome. Complete description of the TME opens the way towards personalized medicine for cancer patients
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Hutchinson, Alexander B. « Identification of response pathways of prostate cancer cell lines in Hans Clevers Media ». Thesis, Queensland University of Technology, 2017. https://eprints.qut.edu.au/103982/4/Alexander%2520Blaine_Hutchinson_Thesis.pdf.
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Prostate cancer has been extremely difficult to grow in vitro, however recent development of a novel media has improved success rates of propagating tumour cells in the laboratory. This project aimed to define pathways regulated by this media in different prostate cancer cells in order to identify critical factors needed for prostate cancer survival. Both common and cell line-specific responses to the media were identified, demonstrating that not all prostate cancer cells respond the same way or have the same requirements. These unique responses must be considered when cells grown in this media are used to explore potential new treatment targets.
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Strong, Nicole Lynette. « Differential regulation of transforming growth factor β signaling by inhibitor of differentiation 1 (ID1) and ID3 in prostate cancer cells ». DigitalCommons@Robert W. Woodruff Library, Atlanta University Center, 2012. http://digitalcommons.auctr.edu/dissertations/450.
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In prostate cancer cells, TGFβ inhibits proliferation in earlier stages of the disease; however the cancer cells become refractory to growth inhibitory effects in advanced stages where TGFβ promotes cancer progression and metastasis. Inhibitor of Differentiation (Id) family of closely related proteins (Id 1- 1d4) are dominant negative regulators and bHLH transcription factors and in general promote proliferation, and inhibit differentiation. In the present study, we have investigated the role of Idi and Id3 proteins in the growth inhibitory effects of TGFβ on prostate cancer cells. The effect of TGF β on proliferation and Idl and Id3 expression were investigated in PZ-HPV7, DU145, and PC3 cells. Idi silencing through siRNA was also used in DU145 and PC3 cells to examine its role in anti-proliferative and migratory effects of TGFβ . TGFβ increased expression of Idi and Id3 in all cell lines followed by a later down regulation of Idi in PZ-HPV7 expression and DU145 cells but not in PC3 cells. Id3 expression remained elevated in all three cell lines. This loss of Idi protein correlated with an increase of CDKNI p21. Id1 knockdown in both DU145 and PC3 cells resulted in decreased proliferation. However, while TGFβ caused a further decrease in proliferation of DU145, but had no further effects in PC3 cells. Knockdown of Id1 or Id3 inhibited TGFβ 1 induced migration in PC3 cells. These findings suggest an essential role of Id1 and Id3 in TGFβ 1 effects on proliferation and migration in prostate cancer cells.
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Guha, Minakshi. « Regulation of Cancer Cell Survival Mediated by Endogenous Tumor Suppression : A Dissertation ». eScholarship@UMMS, 2009. https://escholarship.umassmed.edu/gsbs_diss/431.
Texte intégralRésumé :
Cancer is the second leading cause of death among men and women after heart disease. Though our knowledge associated with the complexities of the cancer network has significantly improved over the past several decades, we have only recently started to get a more complete molecular understanding of the disease. To better comprehend signaling pathways that prevent disease development, we focused our efforts on investigating endogenous tumor suppression networks in controlling effectors of cancer cell survival and proliferation. Survivin is one such effector molecule that controls both cell proliferation and survival. In order to identify how this protein is overexpressed in cancer cells as opposed to normal cells, we looked at signaling molecules that negatively regulate this inhibitor of apoptosis protein. PTEN and caspase 2 are two of the identified proteins that utilize their enzymatic activity to suppress tumor growth by inhibiting downstream cell survival effectors, namely survivin. PTEN uses its phosphatase activity to suppress the PI3K/AKT pathway and maintain cellular homeostasis. In the absence of AKT activity, FOXO transcription factors are able to target downstream gene expression and regulate cell proliferation and survival. Here we have identified survivin as a novel gene target of FOXO, which binds to a specific promoter region of survivin and suppresses its transcription. Alternatively, caspase 2 uses its catalytic activity to suppress survivin gene expression by targeting the NFκB pathway. Caspase 2 acts by cleaving a novel substrate known as RIP1 that prevents NFκB from entering the nucleus, thus inhibiting target gene transcription. Interestingly, survivin is known to be a direct gene target of NFκB that controls cancer cell survival. In our investigation, we found that survivin is downregulated upon caspase 2 activation via the NFκB pathway, resulting in decreased cell cycle kinetics, increased apoptotic threshold and suppressed tumor growth in mice. These studies conclude that survivin is a common effector molecule that is regulated by tumor suppressors to maintain cellular homeostasis. However, upon deactivation of the tumor suppressor pathway, survivin is deregulated and contributes significantly to disease progression. These observations may lead to potential therapeutic implications and novel targeting strategies that will help eradicate harmful cancer cells and spare surrounding healthy cells; often the most persistent problem of most conventional chemotherapy.
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Venugopal, Smrruthi Vaidegi. « Differential Roles of Mammalian Target of Rapamycin Complexes 1 and 2 in Migration of Prostate Cancer Cells ». DigitalCommons@Robert W. Woodruff Library, Atlanta University Center, 2019. http://digitalcommons.auctr.edu/cauetds/189.
Texte intégralRésumé :
In this study, we investigated differential activation and the role of two mTOR complexes in cell migration of prostate cancer cells. Specific knock-down of endogenous RAPTOR and RICTOR by siRNA resulted in decreased cell migration in LNCaP, DU145, and PC3 cells indicating that both mTORC1 and mTORC2 are required for cell migration. EGF treatment induced the activation of both mTORC1 and mTORC2 as determined by complex-specific phosphorylation of mTOR protein. Specific knock-down or inhibition of Rac1 activity in PC3 cells blocked EGF-induced activation of mTORC2, but had no effect on mTORC1 activation. Furthermore, the over-expression of constitutively active Rac1 (Rac1Q61L) resulted in significant increase in cell migration and activation of mTORC2 in PC3 cells, but had no effect on mTORC1 activation. Constitutively active Rac1 (Rac1Q61L) in PC3 cells was localized in the plasma membrane and was found to be in a protein complex which contained mTOR and RICTOR proteins, but not RAPTOR.
In conclusion, we suggested that EGF-induced activation of Rac1 causes the phosphorylation/activation of mTORC2 via RICTOR, specific regulator of mTORC2 activation in numerous cancer cells. The major role played by mTOR in a wide array of cancers has in the recent decades led to the development of numerous mTOR inhibitors. One of the drawback of these first generation mTOR inhibitors are that m TORC1 activity is inhibited but effect on mTORC2 activity require high dosages and prolonged exposure in different cancer cell types including HeLa, PC3, LNCaP, and A549. High dosage of rapamycin and its associated rapalogs required for mTORC2 inhibition is clinically unsuitable. Studies have shown that the dual mTORC1/C2 inhibitors trigger feedback loops causing metastasis and affect the cell viability of normal tissues in vitro and in vivo. There is a need for specific mTORC1 and mTORC2 inhibitor, which overcome the disadvantages of the previously developed mTOR inhibitors. The Rac1-RICTOR axis suggested in this study could be used as a potential target for the development of mTORC2 inhibitor and lead to a potential therapeutic treatment for aggressive prostate cancer.
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Maya-Pineda, Héctor Rubén. « Sensitization of prostate cancer cells to cytotoxic drugs induced by the small adenoviral E1A12S protein through multiple cell death/signalling pathways ». Thesis, Queen Mary, University of London, 2013. http://qmro.qmul.ac.uk/xmlui/handle/123456789/8482.
Texte intégralRésumé :
Replication-selective oncolytic adenoviruses represent a promising anticancer approach with proven efficacy in cancer cell lines and tumour xenografts in vivo. Anti-tumour efficacy, both in preclinical studies and clinical trials, was significantly improved in combination with chemotherapeutics in numerous cancers, including prostate cancer. It has been established that expression of the viral E1A gene is essential for the enhancement of cell killing in combination with cytotoxic drugs. The overall goal of this project is to identify specific E1A gene regions involved in the sensitization to the cytotoxic drugs mitoxantrone and docetaxel, the current standard of care for late stage prostate cancers, to enable the development of improved anti-cancer therapies. Specific regions in the E1A proteins bind to numerous cellular factors to regulate the host cell function and the viral life cycle, including the p300, p400 and pRb family proteins. This work was aimed at determining the mechanisms involved in the synergistic cell killing in prostate cancer cells in response to the combination of the replication-selective (oncolytic) mutant AdΔΔ with cytotoxic drugs. Previous findings suggested an enhancement of drug-induced apoptosis. I found that the small E1A12S protein, unable to induce viral replication, is sufficient to sensitize the prostate cancer cells, 22Rv-1 (AR+), and PC-3 and DU145 (AR-), to drugs. The non-replicating AdE1A12S-mutant AdE1A1104 (defective in p300-binding) could not sensitize the cells while mutants with intact E1A-p300 binding (AdE1A12S, AdE1A1102, AdE1A1108) and defective in p400- (AdE1A1102) or pRb-binding (AdE1A1108) potently sensitized all tested cell lines. In fact, all mutants except AdE1A1104 potently synergised with mitoxantrone and docetaxel to kill the prostate cancer cells. When comparing the non-replicating E1A12S mutants with the corresponding replicating E1A-deletion mutants (expressing E1A12S and 13S) synergy was demonstrated with all replicating mutants except dl1104, which caused an additive effect with mitoxantrone. We hypothesised that the synergistic cell killing is the result of pathway convergence through E1A-p300 and mitoxantrone-activated DNA-damage/apoptosis events. To address this I employed an extensive miRNA array screen to identify potential pathways. Several miRNAs were found to be differentially regulated in response to the combination of AdE1A12S with mitoxantrone compared to each single agent treatment. The majority of these miRNAs are reported to be part of cell death and survival pathways (e.g. apoptosis and autophagy) and to be differentially regulated in prostate cancer. To further investigate the role of these pathways, I determined changes in expression levels of key proteins that had previously been suggested to be targeted by the identified miRNAs, thereby preventing translation of the respective mRNAs. The greatest changes in protein levels in response to AdE1A12S and mitoxantrone were observed for Bcl-2, p-Akt, LC3BII and p62. Finally, I verified similar mechanisms of action when the oncolytic AdΔΔ was combined with mitoxantrone under synergistic conditions. These findings will direct future investigations aimed at dissecting the mechanisms of action for virus-induced sensitization to cytotoxic drugs and may aid in the development of improved therapies for prostate cancer by design of novel oncolytic mutants and combination strategies and/or identification of targets for small molecules inhibitors.
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Kimbrough-Allah, Mawiyah. « Regulation of the PI3-Kinase/PTEN Signaling Pathway by TGF-β in Prostate Cancer Cells ». DigitalCommons@Robert W. Woodruff Library, Atlanta University Center, 2018. http://digitalcommons.auctr.edu/cauetds/123.
Texte intégralRésumé :
Transforming growth factor -β (TGF-β) plays an important role in the progression of prostate cancer. It acts as a tumor suppressor in normal epithelial cells but as a tumor promoter in advanced prostate cancer cells. The PI3-kinase pathway has been shown to play integral roles in many cellular processes including cell proliferation, survival, and cell migration in many cell types. PI3-kinase pathway mediates TGF-β effects on prostate cancer cell migration and invasion. Phosphatase and tensin homolog (PTEN), a tumor suppressor gene, inhibits PI3-kinase pathway and is frequently mutated in prostate cancers. In this present study, we investigated possible roles of PTEN in TGF-β effects on proliferation, migration, and the activation of PI3-kinase/AKT pathway in prostate cancer cells. PTEN was expressed in DU145 cells; however PC3 cells lack PTEN expression. TGF-β1 and TGF-β3 had no effect on PTEN mRNA levels but both isoforms increased PTEN protein levels in DU145 and RWPE1 cells, suggesting that TGF-β may mediate regulation of PTEN protein stability. TGF-β1 and TGF-β3 increased PTEN protein levels even in the presence of cycloheximide, a protein synthesis inhibitor, in DU145 cells. In addition, TGF-β upregulated phosphorylation of PTEN, stabilizing PTEN protein. Increase of PTEN protein levels in these cells may also indicate that PTEN may mediate TGF-β effects on cell proliferation. Knockdown of PTEN in DU145 cells resulted in significant increase in cell proliferation which was no longer affected by TGF-β isoforms. PTEN overexpression in PC3 cells inhibited cell proliferation. Knockdown of endogenous PTEN enhanced cell migration in DU145 cells, whereas PTEN overexpression reduced migration in PC3 cells and reduced phosphorylation of AKT in response to TGF-β. Based on these results, we conclude that PTEN plays a role in inhibitory effects of TGF-β on cell proliferation whereas its absence may enhance TGF-β effects on activation of PI3-kinase pathway and cell migration.
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Carlsson, Björn. « Adoptive T Cell Therapy of Viral Infection and Cancer : Ex vivo Expansion of Cytomegalovirus- and Prostate Antigen-specific T Cells ». Doctoral thesis, Uppsala University, Clinical Immunology, 2005. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-4821.
Texte intégralRésumé :
The main focus of my thesis has been to develop protocols for generating antigen-specific cytotoxic T lymphocytes (CTLs) and T helper cells (TH) for adoptive transfer to treat cytomegalovirus (CMV) disease and prostate cancer. CMV viremia is a severe complication in immunocompromised stem cell transplanted patients. Prostate cancer is a leading cause of death for men in Western countries. Although different in nature, CMV-infected cells and prostate cancer cells can both be eliminated through specific activation of the adaptive immune system.
To generate CMV pp65-specific T cells, I utilized dendritic cells (DCs) modified with an HLA-A*0201/pp65495-503 peptide, a recombinant adenovirus coding for pp65, in vitro transcribed pp65 mRNA and a recombinant pp65 protein. Peptide stimulation yielded large numbers of peptide-specific CD8+ T cells with high lytic activity while adenovirus or mRNA stimulation resulted in the expansion of CTLs against multiple pp65 epitopes. The recombinant protein activated primarily CD4+ TH cells. Stimulation with DCs co-modified with pp65 mRNA and pp65 protein simultaneously generated both pp65-specific CTLs and TH cells. Such T cells would cover all pp65 epitopes while avoiding potential virus related biohazards. The mRNA/protein combinatory approach can be used to stimulate T cells ex vivo from virtually all stem cell donors for adoptive T cell transfer.
I have identified two immunogenic HLA-A*0201-restricted peptide epitopes from the prostate tissue antigen TARP. Repeated stimulations with TARP peptide-pulsed DCs yielded up to 20% TARP-directed CD8+ T cells even when starting from undetectable frequencies (<0.01%). The T cells could be sorted to 99% purity and expanded 1000-fold with retained specificity and activity. We also detected TARP-directed CD8+ T cells in the blood of prostate cancer patients. Therefore, TARP seems to have potential as antigen in DC vaccination or adoptive T cell therapy of prostate cancer.
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Kanda, Naoki. « STAT3 is constitutively activated and supports cell survival in association with survivin expression in gastric cancer cells ». Kyoto University, 2005. http://hdl.handle.net/2433/144746.
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Sanford, Daniel C. « C/EBP delta expression and function in prostate cancer biology ». Columbus, Ohio : Ohio State University, 2006. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=osu1141421403.
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Vaarala, M. (Markku). « Differential gene expression in prostate cancer:identification of genes expressed in prostate cancer, androgen-dependent and androgen-independent LNCaP cell lines, and characterization of TMPRSS2 expression ». Doctoral thesis, University of Oulu, 2000. http://urn.fi/urn:isbn:9514258304.
Texte intégralRésumé :
Abstract
Prostate cancer is the most common solid tumor among men in Western industrialized countries. A major problem in
prostate cancer treatment is the development of androgen-independence, as androgen-deprivation therapy is the basic
therapy for the disease. Molecular mechanisms behind prostate cancer and androgen-independent growth development are
poorly known.
In this study, subtractive hybridization was used for the generation of a cDNA library specific for prostate cancer.
Analysis of the cDNA library revealed over-expression of several ribosomal proteins namely L4, L5, L7a, L23a, L30, L37,
S14 and S18, in prostate cancer cell lines. Over-expression of L7a and L37 was also confirmed in prostate cancer tissue
samples.
Further, cDNA array was used in order to examine differentially expressed genes in androgen-dependent and
androgen-independent prostate cancer cell line LNCaP. Monoamine oxidase A, an Expressed Sequence Tag (EST) similar to rat
P044, and EST AA412049 were highly over-expressed in androgen-dependent LNCaP cells. Tissue-type plasminogen activator,
interferon-inducible protein p78 (MxB), an EST similar to galectin-1, follistatin, fatty acid-binding protein 5, EST
AA609749, annexin I, the interferon-inducible gene 1-8U and phospholipase D1 were highly over-expressed in
androgen-independent LNCaP cells. The EST similar to rat P044, the EST similar to galectin-1, follistatin, annexin I and
the interferon-inducible gene 1-8U were also expressed in benign prostatic hyperplasia tissue. The Y-linked ribosomal
protein S4, Mat-8, and EST AA307912 were highly expressed in benign prostatic hyperplasia tissue.
In situ hybridization of mouse embryos and adult mouse tissues revealed the expression of TMPRSS2 in
the epithelium throughout the gastrointestinal, urogenital and respiratory tracts during development. In human multiple
tissue RNA dot blot, the highest level of expression was detected in prostate, and lower levels in colon, stomach and
salivary gland. TMPRSS2 transcript levels were significantly higher in prostate cancer tissue between benign and
malignant epithelium of prostate cancer patients with untreated disease. Similarly, in poorly differentiated
adenocarcinomas, expression in malignant tissue was significantly higher. Enzymatic mutation detection and direct
sequencing of TMPRSS2 coding region revealed only one deletion in aggressive disease among 9 non-aggressive and 9
aggressive prostate cancer samples. No other mutations were found. Detected 7-base pair deletion leads to premature stop
codon and disruption of serine protease substrate binding and catalytic active site.
We cloned several potential genes whose expression is changed during prostate cancer initiation or progression. These
genes may serve as prostate cancer markers, and further studies are needed to clarify the expression of these proteins
during the disease.
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Bolton, Clement II. « MMP-7 is Required for TGF-β and EGF Induced Migration and Invasion in Prostate Cancer Cells ». DigitalCommons@Robert W. Woodruff Library, Atlanta University Center, 2018. http://digitalcommons.auctr.edu/cauetds/150.
Texte intégralRésumé :
Prostate cancer micrometastasis allows cancer cells to vacate their original tumor sites and migrate to distant parts of the body via the bloodstream, lymphatic system, or by direct extension. Cells synthesize and secrete matrix metalloproteinases (MMPs) that degrade proteins of the surrounding extracellular matrix (ECM); thus allowing them to escape into the lymphatic or circulatory systems to invade other tissues. Transforming growth factor β (TGF-β) induces the migration and invasion of cancer cells and the expression of matrix metalloproteinases (MMPs), specifically MMP-2, and -9 in several malignancies. In this study, we examined the role of MMP-7, a known activator of MMP-2 and MMP-9, in TGF-β signaling in cell proliferation, migration, and invasion in prostate cancer cells. Basal expression levels of MMP7 mRNA, protein, and secreted protein were determined using RT-PCR, western blot analysis, and ELISA, respectively. Our data show that MMP7 mRNA and proteins were differentially expressed in several cell line models representing different stages of prostate cancer. TGF-β1 induces MMP-7 gene expression and protein levels 24 and 48 hours after treatment in PC3 cells. Our data also show that TGF-β induces cell migration and invasion in PC3 and E006AA cells; however, the selective knockdown of MMP7 expression using siRNA resulted in a significant decrease in control and TGFβ-induced cell migration and invasion in both PC3 and E006AA cells. MMP-7 knockdown also caused significant reduction in cell proliferation in PC3 cells. Our data suggest that MMP7 is essential for cell migration and invasion in prostate cancer cells indicating that it may be required for TGFβ-induced cancer metastases.
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Reddivari, Lavanya. « Influence of genetic variability on specialty potato functional components and their effect on prostate cancer cell lines ». [College Station, Tex. : Texas A&M University, 2007. http://hdl.handle.net/1969.1/ETD-TAMU-1330.
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Di, Kaijun, et 狄凱軍. « The role of Id-1 on the proliferation, motility and mitotic regulationof prostate epithelial cells ». Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2007. http://hub.hku.hk/bib/B38944704.
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Ma, Qiuping. « Role of FoxO Factors as the Nuclear Mediator for PTEN-AR Antagonism in Prostate Cancer Cells ». [Tampa, Fla] : University of South Florida, 2008. http://purl.fcla.edu/usf/dc/et/SFE0002559.
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Hassan, Sara. « Epithelial-mesenchymal plasticity in circulating tumour cells from patients with metastatic cancers and PDX models ». Thesis, Queensland University of Technology, 2022. https://eprints.qut.edu.au/228621/8/Sara_Hassan_Thesis.pdf.
Texte intégralRésumé :
There is growing concern about the relevance of epithelial mesenchymal plasticity (EMP) status of primary tumours in influencing their metastatic potential. Circulating tumour cells (CTCs) provide a window into the metastatic process, and molecular characterisation of CTCs could lead to better understanding of the mechanisms involved in the metastatic cascade. This thesis is an investigation of molecular characteristics of EMP in tumours and CTCs using patient-derived xenograft models and patient blood samples. The CTC heterogeneity observed emphasises the complexity in CTC isolation and classification and supports the increasingly recognised importance of the epithelial-mesenchymal hybrid state in cancer progression and metastasis.
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Kobayashi, Takashi. « Activation of Rac1 is closely related to androgen-independent cell proliferation of prostate cancer cells both in vitro and in vivo ». Kyoto University, 2010. http://hdl.handle.net/2433/120918.
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